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Biomedical subjects

J H Chen

Publications and source records attributed to J H Chen.

At least 37 records · Page 2Linked to original sources

Sensitization of dorsal root reflexes in vitro and hyperalgesia in neonatal rats produced by capsaicin.

The maturation of dorsal root reflexes (DRRs) in lumbar roots was characterized in neonatal rats at 1, 2 and 3 weeks after birth using an in vitro isolated spinal cord preparation with attached dorsal roots and dorsal root ganglia (DRG). Changes of DRRs in rats of increasing age were also tested by administration of capsaicin to the DRG and related to spinal mechanisms of hyperalgesia by defining the behavioral responses of neonatal rats to intradermal capsaicin. DRRs evoked by stimulating the adjacent root in 1 week old rats are characterized by highly desynchronized waveforms with power spectra concentrated at frequencies greater than 200 Hz. DRRs in 1 week old rats show very little change in amplitude or area with increasing afferent stimulation strength. In contrast DRRs in 2 and 3 weeks old rats are highly synchronized with power concentrated at frequencies less than 100 Hz and show a graded increase in amplitude and area with increasing stimulus strength. The recovery of DRR amplitude in a paired pulse stimulus protocol is faster in 1 week rats than in 2 or 3 weeks old rats. Finally, DRRs in 2 and 3 week old rats show increased amplitude and area following application of capsaicin to the DRG of the stimulating root whereas those in 1 week old rats do not. These changes parallel the behavioral responses of neonatal rats as 2 and 3 weeks old rats show secondary mechanical hyperalgesia following intradermal capsaicin, but 1 week old rats do not. Our data indicate that the spinal circuitry for DRRs in the neonatal period undergoes rapidly dynamic development in the rat. This development is sufficiently rapid that mechanisms of spinal sensitization induced by capsaicin can be studied in rats 2 weeks old and older.

Aging↗

Atomic imaging in aberration-corrected high-resolution transmission electron microscopy.

In recent years, the successful implementation of a spherical-aberration corrector in a Philips CM 200 FEG ST microscope achieved by Haider et al. has attracted a great deal of attention. However, thus far extensive applications of this novel high-resolution transmission electron microscope (HRTEM) to materials research have been hampered by the problems concerning optimum imaging conditions and image interpretation. In this paper, we present our points of view concerning atomic imaging in an aberration-corrected HRTEM. Since atomic resolution images can also be obtained with other techniques such as through-focus exit-wave function reconstruction (TF-EWR), we have to emphasis that the strength of the aberration-corrected HRTEM particularly lies on its ability to resolve the atomic structure in real time. However, for this purpose it is mandatory that the image contrast be related in a one-to-one function with the projected structure of the object. We analyzed the atomic imaging conditions in much detail and we come to the following conclusion: this novel facility is no doubt a powerful and advanced HRTEM instrument in achieving atomic images with its highest resolution (information limit). We furthermore demonstrate that the combination of the new microscope and TF-EWR will yield optimal results.

Journal Article↗

Comparison of the efficacy and tolerability of telmisartan 40 mg vs. enalapril 10 mg in the treatment of mild-to-moderate hypertension: a multicentre, double-blind study in Taiwanese patients.

The purpose of this randomised, double-blind, double-dummy, parallel-group study was to evaluate the efficacy and tolerability of telmisartan 40 mg once daily vs. enalapril 10 mg once daily in 147 Taiwanese patients with mild-to-moderate essential hypertension (diastolic blood pressure [DBP] 90-109 mmHg). After 6 weeks' treatment, telmisartan produced a significantly greater reduction from baseline in the primary endpoint of trough seated DBP compared with enalapril 10 mg (11.7 vs. 8.7 mmHg, respectively; p = 0.02). Numerically greater reductions compared with baseline in seated systolic blood pressure (SBP), standing DBP, and standing SBP were achieved with telmisartan compared with enalapril. Also, numerically greater proportions of patients achieved blood pressure control (DBP/systolic blood pressure [SBP] <90/140 mmHg) and responded to treatment (reduction from baseline in trough seated DBP > or = 10 mmHg and/or post-treatment DBP <90 mmHg; reduction from baseline in trough seated SBP > or = 10 mmHg and/or post-treatment SBP <140 mmHg) with telmisartan 40 mg compared with enalapril 10 mg. Although both treatments were well tolerated, the incidence of cough was markedly lower with telmisartan 40 mg (8.5%) than with enalapril 10 mg (18.4%) in this population of Taiwanese hypertensive patients.

Adult↗

Induction of VX2 carcinoma in rabbit liver: comparison of two inoculation methods.

Direct injection of VX2 cell suspension into the liver is simple and widely used. Implantation of a fragment of VX2 tumour into the liver using a surgical technique has also been developed in the last decade. In this study, we compared these two methods in order to find a better modality for establishing VX2 liver mass. Forty rabbits, each weighing 2.8-3.2 kg, were divided into two groups, 20 rabbits in each. In Group 1, a tumour cell suspension containing 1 x 10(6) cells in a volume of 0.1 ml, was injected slowly into the liver parenchyma using a 27-gauge needle during laparotomy. In Group 2, a 1 mm(3) fragment of VX2 carcinoma was inoculated into the sub-capsule of the left anterior lobe of the liver. In Group 1, three rabbits showed no tumour growth and 10 rabbits showed evidence of leakage and tumour seeding outside of the liver. In Group 2, all but one rabbit showed tumour growth and none showed evidence of tumour seeding. The leakage rates were 50% and 0% for Group 1 and Group 2, respectively. Overall, the success inoculation rate was 35% for Group 1 and 95% for Group 2. In conclusion, to create the VX2 liver tumour model in rabbits, direct implantation of VX2 tumour fragment into the liver achieved better results than injecting cell suspension of VX2 tumour into the liver.

Animals↗

High-performance liquid chromatographic analysis of bioactive triterpenes in Perilla frutescens.

Perilla frutescens (L.) Britt. (Lamiaceae), a famous traditional Chinese medicine, has been used for the treatment of various diseases. To evaluate the quality of P. frutescens, a simple, rapid and accurate high-performance liquid chromatography (HPLC) method was developed for the assessment of three bioactive triterpene acids: tormentic acid (TA), oleanolic acid (OA) and ursolic acid (UA). The HPLC system used an Spherisob octadecylsilyl silica (ODS) column with acetonitrile and aqueous H(3)PO(4) as the mobile phase and detection at 206 nm. The method was precise with relative standard deviations for these three constituents that ranged between 0.6-1.5% (intraday) and 0.7-2.6% (interday). The content of these three phytochemicals in the leaves of P. frutescens growing at eight different locations of China was determined to establish the effectiveness of the method.

Chromatography, High Pressure Liquid↗

Novel (2E,4E,6Z)-7-(2-alkoxy-3,5-dialkylbenzene)-3-methylocta-2,4,6-trienoic acid retinoid X receptor modulators are active in models of type 2 diabetes.

Previous data have shown that RXR-selective agonists (e.g., 3 and 4) are insulin sensitizers in rodent models of non-insulin-dependent diabetes mellitus (NIDDM). Unfortunately, they also produce dramatic increases in triglycerides and profound suppression of the thyroid hormone axis. Here we describe the design and synthesis of new RXR modulators that retain the insulin-sensitizing activity of RXR agonists but produce substantially reduced side effects. These molecules bind selectively and with high affinity to RXR and, unlike RXR agonists, do not activate RXR homodimers. To further evaluate the antidiabetic activity of these RXR modulators, we have designed a concise and systematic structure-activity relationship around the 2E,4E,6Z-7-aryl-3-methylocta-2,4,6-trienoic acid scaffold. Selected compounds have been evaluated using insulin-resistant rodents (db/db mice) to characterize effects on glucose homeostasis. Our studies demonstrate the effectiveness of RXR modulators in lowering plasma glucose in the db/db mouse model.

Animals↗

Trans-activation of heparanase promoter by ETS transcription factors.

The remodeling of extracellular matrix (ECM) is an important process required for cancer cells to turn into invasive and metastatic cancer cells. To dissolve the protein components of ECM, matrix metalloproteinases are some of the essential enzymes. Another ECM remodeling enzyme is the heparanase (Hpa) that digests the heparin sulfate component of the matrix. In metastatic cancer cells the Hpa gene is upregulated. To investigate the mechanism of why Hpa was upregulated in metastatic cancer cells, the regulatory sequence of heparanase gene was isolated and its function analysed in metastatic breast cancer cells. We found there are four ETS transcription factor binding sites. Two of them flanking the transcription initiation of the Hpa gene are nonfunctional, whereas two others are highly functional and responded to exogenously added ETS transcription factors. Mutation of these two ETS binding sites abolished the transcriptional activation of Hpa promoter by ETS transcription factors. Among four transcription factors tested (ETS1, ETS2, PEA3, and ER81), ETS1 and ETS2 are more potent in transactivating the human Hpa gene. Furthermore, dominant-negative ETS transcription factors failed to transactivate Hpa promoter and could abrogate the function of wild-type transcription factor in transactivation activity of ETS transcription factors on the Hpa promoter. These results suggest that ETS transcription factors play an important role in tumor invasion and metastasis by modulating the remodeling of ECM.

Binding Sites↗

Pinelloside, an antimicrobial cerebroside from Pinellia ternata.

An antimicrobial cerebroside, pinelloside, was isolated from the air-dried tubers of Pinellia ternata (Thunb.) Breit. Its structure was determined as 1-O-beta-D-glucopyranosyl-(2S,3R,4E,11E)-2-(2'R-hydroxyhexadecenoylamino)-4,11-octadecadiene-1,3-diol by chemical transformation and extensive spectroscopic analyses (IR, MS, 1H and 13C NMR, DEPT as well as 2D NMR techniques HMBC, HMQC, 1H-1H COSY and NOESY). The antimicrobial assay showed that this compound was inhibitory to the growth of Bacillus subtilis, Staphylococcus aureus, Aspergillus niger and Candida albicans, with minimum inhibitory concentrations (MICs) of 20, 50, 30 and 10 microg/ml, respectively. The MICs of penicillin G against bacteria B. subtilis, S. aureus, E. coli, P. fluorescens and H. pylori were 0.80, 0.34, 0.56, 1.34 and 0.92, and those of ketoconazole against fungi A. niger, C. albicans and T. rubrum 0.90, 0.65 and 1.0 microg/ml, respectively.

Anti-Infective Agents↗

Fabrication of solid-state nanopores with single-nanometre precision.

Single nanometre-sized pores (nanopores) embedded in an insulating membrane are an exciting new class of nanosensors for rapid electrical detection and characterization of biomolecules. Notable examples include alpha-hemolysin protein nanopores in lipid membranes and solid-state nanopores in Si3N4. Here we report a new technique for fabricating silicon oxide nanopores with single-nanometre precision and direct visual feedback, using state-of-the-art silicon technology and transmission electron microscopy. First, a pore of 20 nm is opened in a silicon membrane by using electron-beam lithography and anisotropic etching. After thermal oxidation, the pore can be reduced to a single-nanometre when it is exposed to a high-energy electron beam. This fluidizes the silicon oxide leading to a shrinking of the small hole due to surface tension. When the electron beam is switched off, the material quenches and retains its shape. This technique dramatically increases the level of control in the fabrication of a wide range of nanodevices.

Crystallization↗

The cerebrosides.

This review covers distribution, structural determination, syntheses and biological activities of the cerebrosides reported so far. Those with absolute stereochemistry assigned are marked herein with '*'. The literature from 1969 to mid-2003 is reviewed and 189 references cited.

Animals↗

Slowing of intestinal transit by fat depends on an ondansetron - sensitive, efferent serotonergic pathway.

The ileal brake is a neural reflex that slows proximal small bowel transit when fat enters the distal small bowel. In rats, ondansetron, a 5-hydroxytryptamine-3 (5-HT3)-receptor antagonist, abolishes the ileal brake. However, the location of this serotonergic pathway is unknown. Of the known enteric sites responsive to 5-hydroxytryptamine (5-HT), only the myenteric neurone is equipped with 5-HT3 receptors and is located on the efferent limb of reflex response. The aim of this study was to test the hypothesis that slowing of intestinal transit by fat may depend on an ondansetron-sensitive serotonergic pathway located on the efferent limb of this reflex response. In a fistulated dog model that compartmentalized the afferent from the efferent limb of the ileal brake response, ondansetron was delivered luminally into the distal (afferent) or proximal (efferent) half of the small bowel to localize the serotonergic pathway. It was found that activating the ileal brake slowed down the proximal intestinal transit to 30% of control values. The ileal brake was abolished when ondansetron was delivered into the proximal but not the distal small bowel. Our data supports the hypothesis that the 5-HT receptors participating in the ileal brake are on the efferent limb of this neural reflex, possibly on myenteric neurones.

Animals↗

Serum lysophosphatidic acid concentrations measured by dot immunogold filtration assay in patients with acute myocardial infarction.

In this study the relation between lysophosphatidic acid (LPA) and myocardial infarction was investigated, the typical and simplified methods for measuring serum LPA concentration by dot immunogold filtration assay (DIFA) based on a polyclonal antibody to LPA were developed, and serum LPA concentrations were measured in 31 patients with acute myocardial infarction (AMI) and 12 controls (blood donors) by DIFA. Serum LPA levels were raised more than twofold 8 h after the onset of AMI. Maximal elevation (10.43 mg/L) was found at 48-72 h following onset and remained higher than the control concentration (1.66 mg/L) 7 days after AMI. The rise in serum LPA concentration in AMI patients suggests that LPA might be involved in AMI-related pathophysiology in the cardiovascular system. The simplified DIFA developed in the present study for measuring serum LPA concentration is convenient and highly sensitive.

Adolescent↗

Expressions of Lewis antigens in human non-small cell pulmonary cancer and primary liver cancer with different pathological conditions.

The expressions of three X series Lewis antigens, including Lewis X (Le(x)), sialyl Lewis X (SLe(x)) and sialyl dimeric Lewis X (SDLe(x)) were studied with immuno-histochemical methods in human non-small cell pulmonary cancer (NSCPC) and primary liver cancer (PLC) with different pathological conditions. The Lewis antigens are mainly expressed on the cell surfaces, medially or slightly in the cytoplasm, but not in the cell nuclei of the cancer tissues. The regions adjacent to the cancer tissues do not express any Lewis antigens. The positive rates of these antigens in NSCPC were within the range of 75% to approximately 86%. There was no apparent difference in positive rates between the cases with different differentiation and the presence or absence of metastasis in peripheral lymph nodes, nor among the three antigens, except that the positive rate of SDLe(x) was lower (about 56%) in the cases with well/medium differentiation and without metastasis. However, the expression-intensities (SI indexes) of all three antigens were significantly higher in the samples of poor differentiation and with metastasis as compared to those with well/medium differentiation and without metastasis. The two sialyl Lewis antigens increased more significantly than non-sialylated Le(x). The expressions of these antigens were also observed in the peripheral lymph nodes with metastasis, but not in those without metastasis. The positive rates of Le(x), SLe(x) and SDLe(x) in human primary liver cancer were 83.3%, 88.9% and 77.8%, respectively. In the cases with cancer cell thrombosis (CCT) in portal vein (an index of metastasis), the expressions of all these three antigens were stronger than those in the cases without CCT. SLe(x) was the most abundant and most highly increased Lewis antigen on the surface of NSCPC and PLC, especially in the cases with poor differentiation and metastasis. In the study of the enzymatic basis of the increased Lewis antigens in PLC by using Northern blot, it was found that the level of alpha1,3 FucT-III/VI mRNA in PLC tissues was much higher than that in the adjacent regions, and more significantly higher in the cancer tissues from patients with CCT in portal vein. In contrast, the expression of alpha1,3 FucT-VII was rather low in cancer tissues and not different from the adjacent regions in spite of the presence or absence of CCT. These results reveal that the SLe(x) in PLC is mainly synthesized by alpha1,3 FucT-III/VI (especially VI) and is the most important Lewis antigen involved in the metastasis of PLC.

Carcinoma, Non-Small-Cell Lung↗

Application of locked intramedullary nails in the treatment of complications after distraction osteogenesis.

Distraction osteogenesis (callotasis) has been widely used in patients with limb-length inequality or massive bone defects. This procedure, however, may be associated with a high incidence of physical and psychosocial complications. Callotasis telescoping on a locked intramedullary nail has been used to shorten the period of external fixation. Little attention has been given to the use of locked intramedullary nails in the treatment of complications after callotasis. Between 1990 and 1999, we used locked intramedullary nailing in 27 patients for the treatment of complications after distraction osteogenesis. There were 17 men and ten women with a mean age of 33.2 years (16 to 66). The nail was inserted at a mean of 3.4 weeks (0 to 15) after removal of the external fixator. Simultaneous autogenous bone grafting and soft-tissue reconstruction were also undertaken in seven and two patients, respectively. There was consolidation of the callus or docking site in all patients at a mean of 6.4 months (2 to 14) after surgery. The mean shortening of the callus was 0.7 cm (0 to 2.5). Two patients had infection at the site of a distal screw which resolved after removal of the nail. In 17 patients the nail was removed at a mean of 26 months after its insertion. Locked intramedullary nails are useful in treating complications after distraction osteogenesis in skeletally mature patients. The risk of infection should be borne in mind.

Adolescent↗

Rottlerin stimulates metallothionein gene expression but inhibits metal transport in Chinese hamster ovary cells.

Metallothionein (MT) can be induced by various metals. We have shown previously that H7, a protein kinase C (PKC) inhibitor, inactivates metal-induced MT gene expression. To investigate whether a specific PKC isoform is involved in the induction process, inhibitors for various PKC isoforms were administered to cadmium-resistant Chinese hamster ovary (Cd(R)) cells. None of the inhibitors used can reduce metal-induced MT gene expression. However, a PKCdelta inhibitor, rottlerin, induced MT mRNA expression in Cd(R) cells in the presence or absence of Cd. Notably, the induction occurs through the activation of the MT transcriptional factor (MTF-1) and is not related to an increase of metal influx. Furthermore, metal accumulation is reduced in the presence of rottlerin. Pulse-labeling analysis indicated that MT protein synthesis increased in Cd(R) cells upon rottlerin treatment. These results suggest that rottlerin blocks metal transport but stimulates MT synthesis in Cd(R) cells. Since rottlerin is capable of reducing the cellular accumulation of Cd, it was expected that the cytotoxic effect of Cd would decrease in the presence of rottlerin. Treating the parental cell of Cd(R) with Cd and rottlerin together indeed showed a decline of cytotoxicity compared to cells treated with Cd alone. We further examined how MTF-1 was activated by rottlerin. Rottlerin-induced MTF-1 activity was not affected in Cd(R) cells by the addition of EDTA. It was, however, diminished by administering an intracellular Zn chelator, TPEN. The result implies a mobilization of intracellular Zn ions after rottlerin treatment in Cd(R) cells. To investigate whether the described results occur in all types of cells, another cell line (GH(3)) was used to study the effect of rottlerin on MT gene expression. The result revealed that rottlerin did not increase the amount of MT mRNA in GH(3) cells. This differential effect between cell lines may be useful for investigating the regulatory mechanism of MT gene expression.

Acetophenones↗